MECHANISM OF MICROTUBULE DYNAMICS REGULATION BY KINESINS

描述(申请人提供)：Kinesin是真核细胞骨架蛋白，以其运动活性而闻名，但它们也是微管(MT)动力学的重要调节因素，MT聚合物的生长或收缩能力。本项目旨在建立运动蛋白超家族成员对微管(MT)动态调节的分子机制。这些动蛋白对MT动力学的调节在多种细胞过程中起着重要作用，如有丝分裂、胞质分裂、神经发育以及纤毛和中心粒长度的控制，但这些动蛋白稳定或破坏MTS的机制尚不完全清楚。我们将通过改变微管蛋白的结构来检验所有这些运动蛋白影响MT动力学的普遍假设，以利于或不利于微管蛋白间接触的形成 它们将MT聚合物结合在一起。为了解决这一假设，我们将使用电子显微镜和其他方法来确定三个模型动蛋白的微管蛋白复合体的结构。该提案有两个总体目标。第一个目的是建立激动素KLP10A和Kar3对MT解聚的作用机制。第二个目的是研究KIF14蛋白对MT的稳定作用机制。

DESCRIPTION (provided by applicant): Kinesins are eukaryotic cytoskeletal proteins best known for their motile activity, but they are also important regulators of microtubule (MT) dynamics, the ability of the MT polymer to grow or shrink. This project seeks to establish the molecular mechanism of microtubule (MT) dynamics regulation by members of the kinesin superfamily. Regulation of MT dynamics by these kinesins play important roles in a variety of cell processes such as mitosis, cytokinesis, neural development and control of cilia and centriole length, but the mechanisms by which these kinesins stabilize or destabilize MTs are not fully clear. We will test the general hypothesis that all these kinesin affect MT-dynamics by modifying the structure of tubulin to favor or disfavor the formation of the inter-tubulin contacts that hold the MT polymer together. To address this hypothesis we will use electron microscopy and other approaches to determine the structure of tubulin complexes of three model kinesins. The proposal has two general aims. The fist aim is to establish the mechanism of MT depolymerization by the kinesins KLP10A and Kar3. The second aim addresses the mechanism of MT stabilization by the kinesin KIF14.